Structure and Genetics of Human Antibodies

Capra, J Donald

Abstract

This is a request for continued support to analyze variable region gene structure in the human immune system. Rheumatoid factors, antibodies to external antigens, and antibodies to other self-reacting components will be studied at the molecular level in order to determine the dynamic range of the human VH repertoire in defined immune responses. Mechanistically, we will study V/J junctional diversity in the human kappa and lambda systems, and D-D and D1-D fusions in the human heavy chain complex. Most of these studies are ongoing and represent extensions of work initiated under the first three years of this project.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Cancer Institute (NCI)
• Type: Research Program Projects (P01)
• Project #: 5P01CA044016-08
• Application #: 5207373
• Support Year: 8
• Fiscal Year: 1996

Publications

Denepoux, S; Razanajaona, D; Blanchard, D et al. (1997) Induction of somatic mutation in a human B cell line in vitro. Immunity 6:35-46

Andris, J S; Miller, A B; Abraham, S R et al. (1997) Variable region gene segment utilization in rhesus monkey hybridomas producing human red blood cell-specific antibodies: predominance of the VH4 family but not VH4-21 (V4-34). Mol Immunol 34:237-53

Li, Y; Spellerberg, M B; Stevenson, F K et al. (1996) The I binding specificity of human VH 4-34 (VH 4-21) encoded antibodies is determined by both VH framework region 1 and complementarity determining region 3. J Mol Biol 256:577-89

Andris, J S; Abraham, S R; Pascual, V et al. (1995) The human antibody repertoire: heavy and light chain variable region gene usage in six alloantibodies specific for human HLA class I and class II alloantigens. Mol Immunol 32:1105-22

Xia, Y; Hwang, L Y; Cobb, M H et al. (1994) Products of the TAL2 oncogene in leukemic T cells: bHLH phosphoproteins with DNA-binding activity. Oncogene 9:1437-46

Potter, K N; Li, Y C; Capra, J D (1994) The cross-reactive idiotopes recognized by the monoclonal antibodies 9G4 and LC1 are located in framework region 1 of two non-overlapping subsets of human VH4 family encoded antibodies. Scand J Immunol 40:43-9

Andris, J S; Brodeur, B R; Capra, J D (1993) Molecular characterization of human antibodies to bacterial antigens: utilization of the less frequently expressed VH2 and VH6 heavy chain variable region gene families. Mol Immunol 30:1601-16

Baer, R (1993) TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell acute leukaemia. Semin Cancer Biol 4:341-7

Potter, K N; Li, Y; Pascual, V et al. (1993) Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment. J Exp Med 178:1419-28

Cai, J; Humphries, C; Lutz, C et al. (1992) Analysis of VH251 gene mutation in chronic lymphocytic leukemia (CLL) and normal B-cell subsets. Ann N Y Acad Sci 651:384-92